Single-cell mechanics provides a sensitive and quantitative means for probing amyloid-β peptide and neuronal cell interactions

By using a highly sensitive technique of atomic force microscopy-based single-cell compression, the rigidity of cultured N2a and HT22 neuronal cells was measured as a function of amyloid-beta 42 (A beta 42) protein treatment. A beta 42 oligomers led to significant cellular stiffening; for example, 90-360% higher force was required to reach 80% deformation for N2a cells. Disaggregated or fibrillar forms of A beta 42 showed much less change. These observations were explained by a combination of two factors: (i) incorporation of oligomer into cellular membrane, which resulted in an increase in the Young's modulus of the membrane from 0.9 +/- 0.4 to 1.85 +/- 0.75 MPa for N2a cells and from 1.73 +/- 0.90 to 5.5 +/- 1.4 MPa for HT22 cells, and (ii) an increase in intracellular osmotic pressure (e.g., from 7 to 40 Pa for N2a cells) through unregulated ion influx. These findings and measurements provide a deeper, more characteristic, and quantitative insight into interactions between cells and A beta 42 oligomers, which have been considered the prime suspect for initiating neuronal dysfunction in Alzheimer's disease.